CAJ | 학술논문

目的：通过研究miR-126在人结肠癌细胞中的表达及其对结肠癌细胞生物学行为的影响，了解miR-126在结肠癌发生发展中的作用。方法：利用原位杂交在高密度人结肠癌组织芯片中研究miR-126的表达，通过慢病毒转染构建miR-126稳定过表达细胞系，并进一步通过体外实验研究miR-126对结肠癌细胞生物学行为的影响。结果：miR-126在人结肠癌组织中表达下调，在存在侵袭转移患者的结肠癌组织中下调尤为明显。miR-126的表达与患者是否发生转移及结肠癌临床分期、Duke’s分期相关(P<0.05)，且miR-126下调越明显，患者预后越差(P=0.025)。利用慢病毒转染构建的miR-126过表达SW480细胞系进行体外实验显示结肠癌细胞中恢复miR-126的表达可抑制结肠癌细胞增殖，使其出现G1期阻滞并促进结肠癌细胞凋亡、抑制结肠癌细胞迁移和侵袭能力。同时miR-126可明显增强结肠癌细胞对化疗药物奥沙利铂的敏感性。进一步生物信息学分析及qRT-PCR结合蛋白免疫印迹法验证IRS1，SLC7A5及TOM1可能为miR-126在结肠癌中的靶基因。结论：miR-126可明显抑制结肠癌的发生发展，且与结肠癌患者预后密切相关，其可能调控的靶基因为IRS1，SLC7A5及TOM1，miR-126有望成为结肠癌临床诊断及治疗的新靶点。
목적：통과연구miR-126재인결장암세포중적표체급기대결장암세포생물학행위적영향，료해miR-126재결장암발생발전중적작용。방법：이용원위잡교재고밀도인결장암조직심편중연구miR-126적표체，통과만병독전염구건miR-126은정과표체세포계，병진일보통과체외실험연구miR-126대결장암세포생물학행위적영향。결과：miR-126재인결장암조직중표체하조，재존재침습전이환자적결장암조직중하조우위명현。miR-126적표체여환자시부발생전이급결장암림상분기、Duke’s분기상관(P<0.05)，차miR-126하조월명현，환자예후월차(P=0.025)。이용만병독전염구건적miR-126과표체SW480세포계진행체외실험현시결장암세포중회복miR-126적표체가억제결장암세포증식，사기출현G1기조체병촉진결장암세포조망、억제결장암세포천이화침습능력。동시miR-126가명현증강결장암세포대화료약물오사리박적민감성。진일보생물신식학분석급qRT-PCR결합단백면역인적법험증IRS1，SLC7A5급TOM1가능위miR-126재결장암중적파기인。결론：miR-126가명현억제결장암적발생발전，차여결장암환자예후밀절상관，기가능조공적파기인위IRS1，SLC7A5급TOM1，miR-126유망성위결장암림상진단급치료적신파점。
Objective:To explore the expression pattern and function of miR-126 in human colon cancer and the underlying mechanisms. <br> Methods:hTe expression pattern of miR-126 in high-density human colon cancer tissue microarray was analyzed by in situ hybridization. Further more, the biological function of miR-126 in colon cancer in vitro was investigated by establishing a stable miR-126 over-expression cell lines. <br> Result:hTe expression of miR-126 was lower in the tumor tissue, especially in metastasis tissue. hTe down-regulation of miR-126 was more obvious in the patients who displayed bad prognosis (P=0.025). Over-expression of miR-126 in colon cancer cell was able to inhibit cell proliferation, promote cell apoptosis and reduce the invasive ability. MiR-126 significantly enhanced the sensitivity of the colon cancer cell to chemotherapeutic drug. It has been shown that IRS1, SLC75A and TOM1 were the potential target genes of miR-126 in colon cancer. <br> Conclusion:MiR-126 was able to inhibit the development of colon cancer and its level was closely related with the prognosis of patients with colon cancer. The potential target genes for miR-126 might include IRS1, SLC7A5 and TOM1. Therefore, miR-126 might be a therapeutic target for colon cancer diagnosis and treatment.